In the influenza virus particle, the genetic material, ribonucleic acid associated with group-specific nucleoprotein, is surrounded by a double membrane consisting of an inner layer of protein and an outer layer of host-derived lipid material. Two glycoproteins, haemagglutinin (HA) and neuraminidase (NA), appear as projections or spikes on the surface of the viral envelope and make up approximately 36% of the total virus. It is well established that these two glycoproteins are the main immunogenic components of the virus and that all other components, including other virus proteins, nucleic acids and lipids, are non-essential for the induction of immunity and yet may lead to undesired side effects and limit to the dosage which can be administered and the level of immunity which can be achieved.
U.S. Pat. No. 4,064,232, assigned to Sandoz Ltd., describes the isolation of the immunogenic components, i.e. the haemagglutinin and neuraminidase, from influenza viruses by selectively solubilizing the components in an aqueous medium with a cationic surfactant and separating the resulting solubilized components from residual sub-viral particles, such as by centrifugation.
The subunit virus has been proposed to be recovered from the aqueous phase by adding treated bio-beads to the aqueous phase, agitating the mixture for about an hour, dialyzing the agitated mixture against a saline solution and then filtering through a straight through sterilizing membrane filter. This procedure is described in U.S. Pat. No. 4,057,626.
Although this latter technique has proved useful in providing purified sub-unit virus vaccines, nevertheless the costs involved are quite high, in that large amounts of highly sophisticated equipment and procedures are necessary, requiring highly skilled and specialized personnel to carry out the process, high capital investments to purchase and build equipment and a large size facility to house the personnel and equipment, high energy use, and high operating costs in the form of chemical, spare parts and filters.